PB2134: THE ROLE OF ADDITIONAL CARBOGEN GAS MIXTURE AND NICOTINAMIDE ON R-CHOP CHEMOTHERAPY IN DLBCL PATIENTS WITH TUMOR HYPOXIA
Authors: D. Rizky, E. A. Pangarsa
Journal: HemaSphere (2022)

Background: Tumor hypoxia increases tumor aggressiveness, immunosuppression, & decreases sensitivity to chemoradiotherapy. The role of tumor hypoxia in DLBCL remains unclear. Hypoxia-inducible factor 1-alpha (HIF-1α) is an oxygen-dependent transcriptional factor that activates several tumor survival pathways. Hypoxia & inflammation have a positive correlation, one is defined by the HIF-1α & NFkB relationship. NFkB involves in cytokine regulations such as TNF-α & sIL-2R. Carbogen gas mixture (95% O2 and 5% CO2) & nicotinamide (an amide of vitamin B3) have been recently studied as a radiosensitizer in solid tumors & also improve tumor oxygenation level. We compared tumor size changes, TNF-α, & sIL-2R serum in DLBCL patients who received carbogen + nicotinamide during chemotherapy R-CHOP versus those who did not. Aims: The primary endpoint was tumor size reduction. Secondary endpoints were changes of TNF-α & sIL2R serum pre-& post-chemotherapy. Tumor MRI was used for examining the size reduction. Methods: This trial is an ongoing single-center, randomized controlled trial. Eligible DLBCL patients who had HIF-1α tissue expression ≥10% were included. Subjects were randomly assigned to the study group (nicotinamide 40 mg/kgBW + carbogen 10 liter/minute during R-CHOP) or control group (R-CHOP) for 1 cycle. Tumor MRI and blood parameters examinations were performed before and 7-days after interventions. Results: Between April-December 2021, 20 patients were enrolled (median age 56.5 years; min & max 21-65 years). For the baseline data, median tumor volume were 152.8 cm3 (4.3-1,542.5 cm3) & 172.2 cm3 (6.4-2,349.7 cm3), median sIL-2R serum were 304 U/mL (24-1,625 U/mL) & 417 U/mL (13-1,897 U/mL), median TNF-α serum were1.95 pg/mL (1.2-4.2 pg/mL) & 1.65 pg/mL (0.8-6.7 pg/mL) in control and subject group respectively, there were no statistically significant differences in these results. Post-chemotherapy, median tumor volume were 34.54 cm3 (1.86-297.5 cm3) & 112 cm3 (1.2-862.98 cm3), there were no significant differences of median Δ tumor size reduction in both groups (-118 cm3 & -85 cm3; p = 0.762) control & subject group respectively. Median sIL-2R serum in control group was increased; 519 U/mL (24-1,557 U/mL) & decreased in subject group; 157 U/mL (13-464 U/mL) although there were no statistically significance (p = 0.314 & p = 0.109 respectively). Median TNF-α serum were 2.1 pg/mL (0.8-6.9 pg/mL) & 1.8 pg/mL (0.4-3.3 pg/mL) in control & subject group respectively (p = 0.671 & p = 0.766). There was a positive correlation between Δ tumor size & Δ sIL-2R serum (p = 0.04 & r = 0.463). 2 patients complaint minor rash & itchy skin. Summary/Conclusion: We found no difference in tumor size reduction between two groups. However, we found a clinical reduction trend of serum sIL-2R in the subject group although it was not statistically significant, this is because of the incomplete sample collection. Serum sIL-2R level also had a positive correlation with tumor size reduction which showed an interesting field of study for the upcoming research.